An indepth understanding of genetic and biochemical regulation in mammalian cells is necessary for understanding of maturation, malignancy, and the aging process. The regulation of purine and pyrimidine biosynthesis in Chinese hamster cells grown in culture will be studied as a model system. Techniques to be employed include: isolation and characterization of mutants, both auxotrophic and regulatory; complementation analysis of mutants; assignment of genes of the pathways to specific human chromosomes by construction of appropriate hybrid cells; analysis of the biochemical defect in each mutant; and analysis of the effects these mutations have on intracellular nucleotide pool sizes and cellular survival in various growth media. Previous work shows that such parameters will be a great importance in the genetic-biochemical regulation of these pathways. Particular emphasis will be placed on study of purine nucleotide interconversion and AMP synthesis from IMP. The information gained in understanding the genetic and biochemical regulation of these two important pathways in somatic mammalian cells should be useful in the understanding of human normal and abnormal developmental processes, including aging. BIBLIOGRAPHIC REFERENCES: Patterson, David. Biochemical Genetics of Chinese Hamster Cell Mutants with Deviant Purine Metabolism IV. Isolation of a Mutant which Accumulates Adenylosuccinic Acid and Succinylaminimidazole Carboxamide Ribotide. Somatic Cell Genetics, 2: 189-203 (1976). Patterson, David and Carol Jones. Biochemical Genetics of Chinese Hamster Cell Mutants with Deviant Purine Metabolism. Isolation, Selection and Characterization of a Mutant Lacking Hypoxanthine-Guanine Phosphoribosyl Transferase (E.C. 2.4.2.8) Activity by Nutritional Means. Somatic Cell Genetics, 2(5): 429-439 (1976).